RhoH, a hematopoietic-specific Rho GTPase, regulates proliferation, survival, migration, and engraftment of hematopoietic progenitor cells
Abstract
Rho guanosine triphosphatases (GT-Pases) are recognized as critical mediators of signaling pathways regulating actin assembly, migration, proliferation, and survival in hematopoietic cells. Here, we have studied a recently identified hematopoietic-specific Rho GTPase, RhoH. Unlike most members of the Rho GTPase family, RhoH is GTPase deficient and does not cycle between GTP- and guanosine diphosphate (GDP)–bound forms, suggesting that regulation of RhoH expression may be critical in its activity. We found that RhoH is expressed in murine hematopoietic progenitor cells (HPCs) and fully differentiated myeloid and lymphoid lineages. In cytokine-stimulated HPCs, knockdown of RhoH expression via RNA interference stimulates proliferation, survival, and stromal cell-derived factor-1α (SDF-1α)–induced migration in vitro. Conversely, RhoH overexpression in these cells via retrovirus-mediated gene transfer is associated with impaired activation of Rac GTPases, reduced proliferation, increased apoptosis, and defective actin polymerization and chemotaxis. In vivo, HPCs with RhoH overexpression demonstrate defective hematopoietic reconstitution capability compared with control vector-transduced cells. Our results suggest that RhoH serves as a negative regulator of both growth and actin-based function of HPCs possibly via suppression of Rac-mediated signaling.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Overexpression of RhoH suppresses Rac1 activity, leading to increased apoptosis.
“While overexpression of RhoH suppresses Rac1 activity thus leading to increased apoptosis (see following paragraph) [27]”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [27]
Low expression levels of RhoH might increase Rac1-induced protection from apoptosis, drug resistance and cause bad prognosis.
“While overexpression of RhoH suppresses Rac1 activity thus leading to increased apoptosis (see following paragraph) [27], low expression levels of RhoH might increase Rac1-induced protection from apoptosis, drug resistance and cause bad prognosis.”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [27]
RhoH regulates the cytoskeleton in haematopoietic cells as an antagonist of Rac1.
“However, more recent studies using bone marrow from RhoH-deficient mice or haematopoietic cells transduced with RhoH showed that RhoH does have an effect in regulation of the cytoskeleton in haematopoietic cells, if only as an antagonist of another Rho GTPase, Rac1 [20,27].”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [27]
High RhoH expression reduces growth and formation of myeloid colonies compared to control cells by half, due to an increase in apoptotic cells.
“In response to stem cell factor (SCF), high RhoH expression levels reduced growth and formation of myeloid colonies compared to control cells by half, due to an increase in apoptotic cells.”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [27]
The percentage of engraftment is severely reduced for RhoH overexpressing cells (approximately 50%).
“Although RhoH transduced donor cells allowed normal distribution of all lineages, the percentage of engraftment was severely reduced for RhoH overexpressing cells (app. 50%).”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [27]
RhoH negatively influences proliferation, migration and engraftment of haematopoietic bone marrow derived progenitor cells.
“Supporting the theory that RhoH acts as a negative regulator of Rac signalling and other signalling cascades, it was found that RhoH negatively influences proliferation, migration and engraftment of haematopoietic bone marrow derived progenitor cells [27].”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [27]
RhoH-transduced cells show reduced Rac1 activity, reduced polarised cortical F-actin staining, and less cell migration in response to SDF-1α.
“RhoH-transduced cells, however, showed reduced Rac1 activity, reduced polarised cortical F-actin staining and less cell migration in response to SDF-1α [27].”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [27]
RhoH overexpression might impair long-term reconstitution of haematopoietic progenitor cells.
“These data indicated that RhoH overexpression might impair long-term reconstitution of haematopoietic progenitor cells.”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [27]
Knockdown of RhoH stimulates proliferation and survival, as well as SDF-1α mediated migration in vivo.
“Conversely, a knockdown of RhoH stimulated proliferation and survival, as well as SDF-1α mediated migration in vivo [27].”
From The small GTPase RhoH is an atypical regulator of haematopoietic cells (2008) · cites this paper as [27]
RHOH is an atypical small GTPase predominantly expressed in hematopoietic cells and plays a vital role in immune function.
“RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function.”
From A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections (2024) · cites this paper as [1]
RHOH exerts a critical role in the activation, development and differentiation of T lymphocytes.
“As a membrane-bound adaptor for proximal protein kinases involved in TCR signal transduction, RHOH exerts a critical role in the activation, development and differentiation of T lymphocytes (1,4).”
From A Novel Homozygous RHOH Variant Associated with T Cell Dysfunction and Recurrent Opportunistic Infections (2024) · cites this paper as [1]
Cites
Cheshier, S. H., Morrison, S. J., Liao, X., & Weissman, I. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3120 · Cited by 858 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
NADPH oxidases: An overview from structure to innate immunity-associated pathologies
Panday, A., Sahoo, M. K., Osorio, D., & Batra, S. (2015) · Cellular & Molecular Immunology · doi:10.1038/cmi.2014.89 · Cited by 944 · see citing works
The small GTPase RhoH is an atypical regulator of haematopoietic cells
Fueller, F., & Kubatzky, K. F. (2008) · Cell Communication and Signaling · doi:10.1186/1478-811x-6-6 · Cited by 40 · see citing works
Zhou, J., Qian, M., Jiang, N., Wu, J., Feng, X., Yu, M., Min, Q., Xu, H., Yang, Y., Yang, Q., et al. (2024) · Journal of Clinical Immunology · doi:10.1007/s10875-024-01735-4 · Cited by 4 · see citing works
- Authors
- Gu, Y., Jasti, A. C., Jansen, M., & Siefring, J. E.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- ORCID
- Gu, Yi
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-02-15
- Volume
- 105
- Issue
- 4
- Pages
- 1467-1475
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2158510222
- Cited by
- 106
- References
- 1
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2022: 5 · 2021: 1 · 2020: 5 · 2019: 4 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 7 · 2012: 7
- FWCI
- 4.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- RhoH, Rho GTPases, hematopoietic progenitor cells, hematopoietic recovery, cell proliferation, apoptosis, cell migration, chemotaxis, actin polymerization, SDF-1α, stromal cell-derived factor-1α
- MeSH terms
- Actins, Amino Acid Sequence, Animals, Cell Line, Cell Movement, Cell Survival, Cloning, Molecular, Enzyme Repression, Graft Rejection, Growth Inhibitors, Hematopoietic Stem Cells, Male, Molecular Sequence Data, Protein Processing, Post-Translational, Transcription Factors, Down-Regulation, Apoptosis, Hematopoietic Stem Cell Transplantation, rho GTP-Binding Proteins, rac GTP-Binding Proteins, Cell Proliferation, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
